Early childhood caries (ECC) is the most prevalent chronic childhood disease in the U.S., particularly among economically disadvantaged, underserved children. We propose to continue our existing Center to Address Disparities in Children's Oral Health (U54DE014251) and its efforts to understand, prevent, and reduce oral health disparities, with a focus on preventing ECC. The themes of our collaborative, community-based program are (1) to provide the high-quality evidence base for new methods to prevent ECC in populations experiencing oral-health disparities and (2) to identify the most effective dissemination methods for delivering fluoride varnish (FV), an efficacious preventive method. We will actively engage California communities and providers in two large-scale intervention studies utilizing randomized clinical trial (RCT) methodology, stratified by settings, to assess the effectiveness or clinical efficacy of different preventive methods on caries incidence and increment among low-income children. Using the RE-AIM framework, Project 1 will identify the most effective setting (medical, social service agency or dental) to disseminate FV to the greatest number of 1-3-year-old children. Stratifying on setting, a parallel groups practical RCT will be conducted in 24 community-based primary care clinics (CPCCs) from the UCSF primary care collaborative research network, and 24 California Special Supplemental Nutrition Programs for Women, Infants and Children (WICs). Each non-dental site (CPCC or WIC) will be randomized to a program of parental counseling and onsite FV application or to parental counseling and referral to a dentist for child's FV application. We will also compare two automated telephone counseling methods and utilize teledentistry approaches for blinded caries assessments. Project 2 is an intervention study to be conducted in dental and non-dental settings, both affiliated with Federally Qualified Health Centers near the US-Mexico border, to compare the relative caries prevention efficacy of four protocols in 3-6 year-old children: 1) parental oral-health counseling (C) alone;2) C+ FV;3) C+ fluoride-releasing, glass ionomer (Gl) sealants applied to primary molars, and 4) C+FV+ Gl. Our Administrative Core, Statistics and Data Coordinating Center, and Community Liaison Program will support our two RCTs and developmental projects. These endeavors, with other education and career development activities, will foster new investigators to increase oral-health-disparity research capacity.